OBI 814 - Estus Lecture 4 - Exam 2

• Sensory physiology involves how sensory systems signal stimulus strength, two-point discrimination tests, lateral inhibition, adaptation roles, TRP channel sensations, anesthesia, pain-related terms, medial lemniscus and lateral spinothalamic pathways, peripheral sensitization, pain reduction via rubbing, descending inhibition, and opiate factors

Overview of Sensory Pathways

• Most sensory pathways project to the thalamus and relay information to cortical centers
• Olfaction is an exception, projecting to the olfactory bulb and cortex
• Cortical areas analyze sensory information from the contralateral side of the body

Sensory Systems

• Somatosensory system detects external touch and heat stimuli
• Viscerosensory system detects internal stretch, pressure, and pain, usually perceived after infection, inflammation, or extreme distension
• The system also includes olfaction (smell), gustatory (taste),visual, auditory, and vestibular senses (balance)

Types of Sensory Neurons

• Sensory neurons include free nerve endings, enclosed nerve endings, and specialized receptor cells
• Free nerve endings include pain neurons
• Enclosed nerve endings include Pacinian corpuscles
• Specialized receptor cells include those for hearing, vision, and taste, and their first-order neurons are not DRGs

General Information Relay

• Sensory receptors detect stimuli and act as transducers to create intracellular signals and membrane potential changes
• Receptor potential: Change in sensory receptor membrane potential
• In neurons, depolarization crosses a threshold, causing an action potential to the CNS
• Non-neuron receptors signal adjacent neurons to modify their action potential (AP)
• Information is relayed through a hierarchical series of neurons to CNS

Coding of Sensory Information

• The stimulus duration is coded by action potential volley
• The intensity is coded by action potential frequency and the number of neurons signaling

Receptor Potential Properties

• A graded membrane potential is generated by environmental stimuli
• It spreads locally, decreasing over time and stimulus distance
• The potential is proportional to the strength of the stimulus
• Multiple graded potentials can summate with time through repetitive stimuli, and in space, multiple stimuli hit different axon branches

Perceptual Threshold

• Perceptual threshold refers to the level of stimulus needed to be aware of a particular sensation
• Absolute threshold is sensitivity when the system is responsive, such as 50 photons needed in a dark-adapted eye
• Relative threshold is the system's sensitivity varying, where prior stimulation reduces current sensitivity, and lack of prior stimulation increases current sensitivity

Receptive Fields

• Area innervated by sensory receptors
• It varies in size with the receptor type and neuron branching degree
• Smaller fields mean an increased ability to localize stimuli

Sensory Stimulus and Two-Point Discrimination

• Resolution in a two-point test: points in two fields are detected separately, two points in one field are detected as one
• Neighbors in periphery are neighbors in the CNS, following a "Modality"-o-topic map
• Olfaction is an exception

Enhancing Stimulus Localization

• Inhibitory interneurons reduce signaling in pathways parallel to the primary stimulus pathway
• Thus increasing contrast and ability to localize stimuli

Adaptation - Response to Signal

• Rapid receptors detect changes and inform us when conditions are changing, but do not maintain a constant signal
• Slow receptors provide continual indication of a sensory stimulus, such as proprioception or blood pressure
• Mechanisms involve receptor/system variations like pupil contraction/dilation, receptor modification, and Pacinian corpuscle fluid shifts

Somatosensory System

• Touch, temperature, pain and proprioception are all submodalities

Transduction of touch

• Pressure distorts sensory membrane, opening Na+ channels, resulting in Na+ influx and local graded membrane potential
• Influx continues as long as the stimulus is applied
• Intense deformation =greater depolarization
• Action potential is generated if graded potentials reach or summate to the threshold
• A stimulus' intensity is coded by action potential frequency and the number of receptor fields

Receptor cells

• Merkel cells sense pressures and textures that are steady
• Meissner's corpuscles respond to flutter and stroking movements
• Ruffini corpuscles respond to skin stretch
• Pacinian corpuscles sense vibration
• Free nerve endings respond to noxious stimuli

Touch and pressure receptor adaptations

• Rapidly adapting receptors adapt quickly
• Slowly adapting receptors adapt slowly

Evolutionary Advanced Receptors

• Neurons with more evolutionary advanced receptors tend to have larger, myelin axons
• Aα fibers serve touch, pressure, and vibration sensation
• C fibers serve temperature and pain sensation

TRP (Transient Receptor Potential) Channels

• Common somatosensory receptors that have six transmembrane domains
• Act as functional homotetramer units
• Exhibit Polymodality, responding to multiple stimuli

Thermal receptors

• Form a TRP family that terminate in subcutaneous layers
• Cold receptors are activated by a body temperature decrease
• Warm receptors are activated by a body temperature increase
• TRPV1, TRPM8, TRPA1, TRPV3, and TRPV4 are thermal receptors

Thermal Receptor Data

• AP rate is measured through the thermal neuron axon in skin
• With basal action at 32 degrees C increases with a decrease to 30C, then adapts slightly faster
• When temperature returns to 32C, AP frequency returns to baseline

Somatosensory Pathways

• Signals from the system reach the brain via the medial lemniscus pathway and the lateral spinothalamic tract
• More evolutionary receptors utilize the medial lemniscus pathway
• Primitive receptors utilize the lateral spinothalamic tract

Medial Lemniscus Pathway

• Advanced receptors, larger fibers, ~110 m/sec AP speed, and brainstem crossover

Lateral Spinothalamic Tract

• Primitive receptors, smaller fibers, ~60 m/sec AP speed, and point of entry crossover

Somatosensory Cortex

• The homunculus represents tissue cortex proportion in different species
• Sensory coding interpretation is a learned process

Lidocaine impact on action potentials

• Lidocaine inhibits voltage-gated Na+ channels

Capsaicin Receptor

• Capsaicin binds TRPV1 channels, also stimulated by heat

Menthol receptor

• Stimulates TRPM8, to also signal cool temperatures

Defining Pain

• Pain is a psychological, social, genetic, and biological composite that requires comprehensive management

Clinical Pain Terminology

• Anesthesia: Loss of sensation
• Dysesthesia: Altered sensation
• Analgesia: Relief of pain
• Sensitization: Increased pain sensitivity
• Allodynia: Sensitivity to non-painful stimulus
• Central pain: Sensitization in CNS

Nociception Terminology

• Concerns noxious stimuli transduction by Nociceptors, like converting stimuli into neuronal action potentials
• Mechanoreceptors transduce mechanical pressure
• Chemoreceptors respond to H+ and chemicals
• Polymodal nociceptors respond to mechanical, thermal, or chemical information

Types of Pain

• Somatic results from painful stimuli; neuropathic results actual nerve damage from neuropathy, injury, cancer, or stroke
• There is also continuous, episodic, acute, chronic, and referred pain

Pain transduction

• Peripheral Sensitization: Nociceptors activated/sensitized through histamine and tissue damage products
• Peripheral Sensitization is increased pain
• Spinal cord, CGRP, DRG, and trigeminal dorsal horn components
• CGRP and substance P dilate blood vessels
• Histamine contributes to edema

Trigeminal Nerve

• Carries sensory inputs: skin, oral, teeth, cranial vessels, muscle and TMJ
• Signals to the Spinal Trigeminal Nucleus, then the Thalamus, and finally the Somatosensory Cortex

Gate Control Theory

• Non-painful stimulus competing through inhibitory interneurons reduces pain pathway signaling

Descending Inhibition and Pain Transmission

• Pain transmission countered by descending inhibition
• Endogenous Analgesia blocks transmission to stop pain
• Opiate neurotransmitters, receptors, exogenous morphine involved

Endogenous Pain Control

• Involves brainstem axons modulating pain via opiate interneurons in the brainstem/spinal cord
• Neuropeptides act as opioid pain inhibitors in the spinothalamic tract

Pain Pharmacology

• Treatments include anti-inflammatory agents, calcium channel blockers, anticonvulsants, and opiates
• Chronic pain is one lasting beyond usual healing time, persists over three months, is stressful, intractable, and a lead cause of disability

Opioids

• Used for managing chronic neuropathic pain
• Long-acting: Oxycodone, morphine, methadone, fentanyl, oxymorphone, buprenorphine
• Impacts: Loss of enjoyment, concentration, energy, ability to sleep well, increased depression

Referred Pain

• The visceral pain system refers pain, and an accurate pain origin can be predicted from the site
• Visceral and somatic convergent afferent converge on secondary neurons
• The brain mistakenly identifies the sensation with the peripheral structure

Referred Pain and Myocardial Infarcts

• Men tend to have vessel disease (left side of heart) where clots are felt in the chest and left arm
• Women tend to have vessel disease (right side of heart) where clots are felt as GI pain/nausea

Raynaud phenomenon

• Sympathetic ganglia serving the fingers are located in the hand
• One experiencing it may find relief in an a-adrenergic inhibitor.